Physical Chemistry

Following Molecular Mobility During Chemical Reactions: No Evidence for Active Propulsion

Authors

Abstract

The measured changes in self-diffusion of small molecules during reactions have been attributed “boosted mobility”. We demonstrate the critical role of changing concentrations of paramagnetic ions on nuclear magnetic resonance (NMR) signal intensities, which lead to erroneous measurements of diffusion coefficients. We present simple methods to overcome this problem. The use of shuffled gradient amplitudes allows accurate diffusion NMR measurements, even with time-dependent relaxation rates caused by changing concentrations of paramagnetic ions. The addition of a paramagnetic relaxation agent allows accurate determination of both diffusion coefficients and reaction kinetics during a single experiment. We analyze a copper-catalyzed azide-alkyne cycloaddition ‘click’ reaction, for which boosted mobility has been claimed. With our methods, we accurately measure the diffusive behavior of solvent, starting materials and product, and find no global increase in diffusion coefficients during the reaction. We overcome NMR signal overlap using an alternative reducing agent to improve the accuracy of the diffusion measurements. The alkyne reactant diffuses slower as the reaction proceeds, due to binding to the copper catalyst during the catalytic cycle. The formation of this intermediate was confirmed by complementary NMR techniques and density functional theory calculations. Our work calls into question recent claims that molecules actively propel or swim during reactions, and establishes that time-resolved diffusion NMR measurements can provide valuable insight into reaction mechanisms.

Content

Thumbnail image of Manuscript.pdf

Supplementary material

Thumbnail image of SI.pdf
Electronic Supporting Information
Experimental details, NMR spectra, processed NMR data.
Thumbnail image of 2) Static T1 measurements.zip
2) Static T1 measurements
Raw and processed NMR data for static T1 measurements (summarised in Table S3-4).
Thumbnail image of 5) Gradients on and off.zip
5) Gradients on and off
Raw and processed NMR data for diffusion experiments with gradients 'on' and 'off' (Figure 3b-d).
Thumbnail image of Read me.txt
Read me
Details of the raw data uploaded, directions on where to find gradient calibration details (essential prior to data processing).
Thumbnail image of 1) Static diffusion measurements (1 of 2).zip
1) Static diffusion measurements (part 1/2)
Raw and processed diffusion NMR data for static samples (part 1/2).
Thumbnail image of 1) Static diffusion measurements (2 of 2).zip
1) Static diffusion measurements (part 2/2)
Raw and processed diffusion NMR data for static samples (part 2/2).
Thumbnail image of 3) Reaction diffusion measurements.zip
3) Reaction diffusion measurements (part 1/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 1/30)
Thumbnail image of 3) Reaction diffusion measurements.z01
3) Reaction diffusion measurements (part 2/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 2/30)
Thumbnail image of 3) Reaction diffusion measurements.z02
3) Reaction diffusion measurements (part 3/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 3/30)
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3) Reaction diffusion measurements (part 4/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 4/30)
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3) Reaction diffusion measurements (part 5/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 5/30)
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3) Reaction diffusion measurements (part 6/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 6/30)
Thumbnail image of 3) Reaction diffusion measurements.z06
3) Reaction diffusion measurements (part 7/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 7/30)
Thumbnail image of 3) Reaction diffusion measurements.z07
3) Reaction diffusion measurements (part 8/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 8/30)
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3) Reaction diffusion measurements (part 9/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 9/30)
Thumbnail image of 3) Reaction diffusion measurements.z09
3) Reaction diffusion measurements (part 10/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 10/30)
Thumbnail image of 3) Reaction diffusion measurements.z10
3) Reaction diffusion measurements (part 11/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 11/30)
Thumbnail image of 3) Reaction diffusion measurements.z11
3) Reaction diffusion measurements (part 12/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 12/30)
Thumbnail image of 3) Reaction diffusion measurements.z12
3) Reaction diffusion measurements (part 13/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 13/30)
Thumbnail image of 3) Reaction diffusion measurements.z13
3) Reaction diffusion measurements (part 14/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 14/30)
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3) Reaction diffusion measurements (part 15/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 15/30)
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3) Reaction diffusion measurements (part 16/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 16/30)
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3) Reaction diffusion measurements (part 17/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 17/30)
Thumbnail image of 3) Reaction diffusion measurements.z17
3) Reaction diffusion measurements (part 18/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 18/30)
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3) Reaction diffusion measurements (part 19/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 19/30)
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3) Reaction diffusion measurements (part 20/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 20/30)
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3) Reaction diffusion measurements (part 21/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 21/30)
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3) Reaction diffusion measurements (part 22/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 22/30)
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3) Reaction diffusion measurements (part 23/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 23/30)
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3) Reaction diffusion measurements (part 24/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 24/30)
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3) Reaction diffusion measurements (part 25/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 25/30)
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3) Reaction diffusion measurements (part 26/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 26/30)
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3) Reaction diffusion measurements (part 27/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 27/30)
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3) Reaction diffusion measurements (part 28/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 28/30)
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3) Reaction diffusion measurements (part 29/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 29/30)
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3) Reaction diffusion measurements (part 30/30)
Raw and processed diffusion NMR data obtained during the click reaction (part 30/30)
Thumbnail image of 4) Chemical shift analysis 1) Reaction - Experiment 25 - MNova.zip
4) Chemical shift analysis 1) Reaction - Experiment 25 MNova
Processed NMR data for Experiment 25, used for 1H chemical shift analysis
Thumbnail image of 4) Chemical shift analysis 1) Reaction - Experiment 25 - NMR data.z01
4) Chemical shift analysis 1) Reaction - Experiment 25 NMR data (part 1/2)
Raw NMR data for Experiment 25, used for 1H chemical shift analysis (part 1/2)
Thumbnail image of 4) Chemical shift analysis 1) Reaction - Experiment 25 - NMR data.zip
4) Chemical shift analysis 1) Reaction - Experiment 25 NMR data (part 2/2)
Raw NMR data for Experiment 25, used for 1H chemical shift analysis (part 2/2)
Thumbnail image of 4) Chemical shift analysis 1) Reaction - Experiment 26.zip
4) Chemical shift analysis 1) Reaction - Experiment 26
Raw and processed NMR data for Experiment 26, used for 13C chemical shift analysis
Thumbnail image of 4) Chemical shift analysis 2) Titration - Experiment 27.zip
4) Chemical shift analysis 2) Titration - Experiment 27
Raw and processed NMR data for Experiment 27, used for 1H and 13C chemical shift analysis
Thumbnail image of 6) T1 during reaction 1) Without Gd-DTPA - Experiment 30, 31, 32 (Figure 3) - Germany.zip
6) T1 during reaction 1) Without Gd-DTPA - Experiment 30, 31, 32 - Germany
Raw and processed NMR data for time-resolved NMR T1 measurements during the click reaction. Data from Germany, Experiments 30-32 used in Figure 3a
Thumbnail image of 6) T1 during reaction 1) Without Gd-DTPA - Experiment 33 MNova.rar
6) T1 during reaction 1) Without Gd-DTPA - Experiment 33 MNova
Processed NMR data for Experiment 33, time-resolved NMR T1 measurements during the click reaction.
Thumbnail image of 6) T1 during reaction 1) Without Gd-DTPA - Experiment 33 raw NMR data.zip
6) T1 during reaction 1) Without Gd-DTPA - Experiment 33 raw NMR
Raw NMR data for Experiment 33, time-resolved NMR T1 measurements during the click reaction.
Thumbnail image of 6) T1 during reaction 1) Without Gd-DTPA - Experiment 34 MNova.zip
6) T1 during reaction 1) Without Gd-DTPA - Experiment 34 MNova
Processed NMR data for Experiment 34, time-resolved NMR T1 measurements during the click reaction.
Thumbnail image of 6) T1 during reaction 1) Without Gd-DTPA - Experiment 34 raw NMR data.zip
6) T1 during reaction 1) Without Gd-DTPA - Experiment 34 raw NMR
Raw NMR data for Experiment 34, time-resolved NMR T1 measurements during the click reaction.
Thumbnail image of 6) T1 during reaction 1) Without Gd-DTPA - Experiment 35 MNova.rar
6) T1 during reaction 1) Without Gd-DTPA - Experiment 35 MNova
Processed NMR data for Experiment 35, time-resolved NMR T1 measurements during the click reaction.
Thumbnail image of 6) T1 during reaction 1) Without Gd-DTPA - Experiment 35 raw NMR data.zip
6) T1 during reaction 1) Without Gd-DTPA - Experiment 35 raw NMR
Raw NMR data for Experiment 35, time-resolved NMR T1 measurements during the click reaction.
Thumbnail image of 6) T1 during reaction 2)  With Gd-DTPA - Experiment 36 MNova.zip
6) T1 during reaction 2) With Gd-DTPA - Experiment 36 MNova
Processed NMR data for Experiment 36, time-resolved NMR T1 measurements during the click reaction, with Gd-DTPA added
Thumbnail image of 6) T1 during reaction 2)  With Gd-DTPA - Experiment 36 raw NMR.zip
6) T1 during reaction 2) With Gd-DTPA - Experiment 36 raw NMR
Raw NMR data for Experiment 36, time-resolved NMR T1 measurements during the click reaction, with Gd-DTPA added
Thumbnail image of 6) T1 during reaction 2)  With Gd-DTPA -Experiment 37 MNova.rar
6) T1 during reaction 2) With Gd-DTPA - Experiment 37 MNova
Processed NMR data for Experiment 37, time-resolved NMR T1 measurements during the click reaction, with Gd-DTPA added
Thumbnail image of 6) T1 during reaction 2)  With Gd-DTPA -Experiment 37 raw NMR data.zip
6) T1 during reaction 2) With Gd-DTPA - Experiment 37 raw NMR
Raw NMR data for Experiment 37, time-resolved NMR T1 measurements during the click reaction, with Gd-DTPA added
Thumbnail image of 6) T1 during reaction 2)  With Gd-DTPA -Experiment 38 MNova.zip
6) T1 during reaction 2) With Gd-DTPA - Experiment 38 MNova
Processed NMR data for Experiment 38, time-resolved NMR T1 measurements during the click reaction, with Gd-DTPA added
Thumbnail image of 6) T1 during reaction 2)  With Gd-DTPA -Experiment 38 raw NMR data.zip
6) T1 during reaction 2) With Gd-DTPA - Experiment 38 raw NMR
Raw NMR data for Experiment 38, time-resolved NMR T1 measurements during the click reaction, with Gd-DTPA added